Comprehensive Multimodal Deep Learning Survival Prediction Enabled by a Transformer Architecture: A Multicenter Study in Glioblastoma

Background: This research aims to improve glioblastoma survival prediction by integrating MR images, clinical and molecular-pathologic data in a transformer-based deep learning model, addressing data heterogeneity and performance generalizability. Method: We propose and evaluate a transformer-based non-linear and non-proportional survival prediction model. The model employs self-supervised learning techniques to effectively encode the high-dimensional MRI input for integration with non-imaging data using cross-attention. To demonstrate model generalizability, the model is assessed with the time-dependent concordance index (Cdt) in two training setups using three independent public test sets: UPenn-GBM, UCSF-PDGM, and RHUH-GBM, each comprising 378, 366, and 36 cases, respectively. Results: The proposed transformer model achieved promising performance for imaging as well as non-imaging data, effectively integrating both modalities for enhanced performance (UPenn-GBM test-set, imaging Cdt 0.645, multimodal Cdt 0.707) while outperforming state-of-the-art late-fusion 3D-CNN-based models. Consistent performance was observed across the three independent multicenter test sets with Cdt values of 0.707 (UPenn-GBM, internal test set), 0.672 (UCSF-PDGM, first external test set) and 0.618 (RHUH-GBM, second external test set). The model achieved significant discrimination between patients with favorable and unfavorable survival for all three datasets (logrank p 1.9\times{10}^{-8}, 9.7\times{10}^{-3}, and 1.2\times{10}^{-2}). Conclusions: The proposed transformer-based survival prediction model integrates complementary information from diverse input modalities, contributing to improved glioblastoma survival prediction compared to state-of-the-art methods. Consistent performance was observed across institutions supporting model generalizability.

Fourier PD and PDUNet: Complex-valued networks to speed-up MR Thermometry during Hypterthermia

Hyperthermia (HT) in combination with radio- and/or chemotherapy has become an accepted cancer treatment for distinct solid tumour entities. In HT, tumour tissue is exogenously heated to temperatures of 39 to 43 $\degree$C for 60 minutes. Temperature monitoring can be performed noninvasively using dynamic magnetic resonance imaging (MRI). However, the slow nature of MRI leads to motion artefacts in the images due to the movements of patients during image acquisition time. By discarding parts of the data, the speed of the acquisition can be increased - known as Undersampling. However, due to the invalidation of the Nyquist criterion, the acquired images have lower resolution and can also produce artefacts. The aim of this work was, therefore, to reconstruct highly undersampled MR thermometry acquisitions with better resolution and with less artefacts compared to conventional techniques like compressed sensing. The use of deep learning in the medical field has emerged in recent times, and various studies have shown that deep learning has the potential to solve inverse problems such as MR image reconstruction. However, most of the published work only focusses on the magnitude images, while the phase images are ignored, which are fundamental requirements for MR thermometry. This work, for the first time ever, presents deep learning based solutions for reconstructing undersampled MR thermometry data. Two different deep learning models have been employed here, the Fourier Primal-Dual network and Fourier Primal-Dual UNet, to reconstruct highly undersampled complex images of MR thermometry. It was observed that the method was able to reduce the temperature difference between the undersampled MRIs and the fully sampled MRIs from 1.5 $\degree$C to 0.5 $\degree$C.

Benchmarking ChatGPT-4 on ACR Radiation Oncology In-Training Exam (TXIT): Potentials and Challenges for AI-Assisted Medical Education and Decision Making in Radiation Oncology

The potential of large language models in medicine for education and decision making purposes has been demonstrated as they achieve decent scores on medical exams such as the United States Medical Licensing Exam (USMLE) and the MedQA exam. In this work, we evaluate the performance of ChatGPT-3.5 and ChatGPT-4 in the specialized field of radiation oncology using the 38th American College of Radiology (ACR) radiation oncology in-training exam (TXIT). ChatGPT-3.5 and ChatGPT-4 have achieved the scores of 63.65% and 74.57%, respectively, highlighting the advantage of the latest ChatGPT-4 model. Based on the TXIT exam, ChatGPT-4's strong and weak areas in radiation oncology are identified to some extent. Specifically, ChatGPT-4 demonstrates good knowledge of statistics, CNS & eye, pediatrics, biology, and physics but has limitations in bone & soft tissue and gynecology, as per the ACR knowledge domain. Regarding clinical care paths, ChatGPT-4 performs well in diagnosis, prognosis, and toxicity but lacks proficiency in topics related to brachytherapy and dosimetry, as well as in-depth questions from clinical trials. While ChatGPT-4 is not yet suitable for clinical decision making in radiation oncology, it has the potential to assist in medical education for the general public and cancer patients. With further fine-tuning, it could assist radiation oncologists in recommending treatment decisions for challenging clinical cases based on the latest guidelines and the existing gray zone database.

The Segment Anything foundation model achieves favorable brain tumor autosegmentation accuracy on MRI to support radiotherapy treatment planning

Background: Tumor segmentation in MRI is crucial in radiotherapy (RT) treatment planning for brain tumor patients. Segment anything (SA), a novel promptable foundation model for autosegmentation, has shown high accuracy for multiple segmentation tasks but was not evaluated on medical datasets yet. Methods: SA was evaluated in a point-to-mask task for glioma brain tumor autosegmentation on 16744 transversal slices from 369 MRI datasets (BraTS 2020). Up to 9 point prompts were placed per slice. Tumor core (enhancing tumor + necrotic core) was segmented on contrast-enhanced T1w sequences. Out of the 3 masks predicted by SA, accuracy was evaluated for the mask with the highest calculated IoU (oracle mask) and with highest model predicted IoU (suggested mask). In addition to assessing SA on whole MRI slices, SA was also evaluated on images cropped to the tumor (max. 3D extent + 2 cm). Results: Mean best IoU (mbIoU) using oracle mask on full MRI slices was 0.762 (IQR 0.713-0.917). Best 2D mask was achieved after a mean of 6.6 point prompts (IQR 5-9). Segmentation accuracy was significantly better for high- compared to low-grade glioma cases (mbIoU 0.789 vs. 0.668). Accuracy was worse using MRI slices cropped to the tumor (mbIoU 0.759) and was much worse using suggested mask (full slices 0.572). For all experiments, accuracy was low on peripheral slices with few tumor voxels (mbIoU, <300: 0.537 vs. >=300: 0.841). Stacking best oracle segmentations from full axial MRI slices, mean 3D DSC for tumor core was 0.872, which was improved to 0.919 by combining axial, sagittal and coronal masks. Conclusions: The Segment Anything foundation model, while trained on photos, can achieve high zero-shot accuracy for glioma brain tumor segmentation on MRI slices. The results suggest that Segment Anything can accelerate and facilitate RT treatment planning, when properly integrated in a clinical application.

Deep Learning for automatic head and neck lymph node level delineation

Background: Deep learning-based head and neck lymph node level (HN_LNL) autodelineation is of high relevance to radiotherapy research and clinical treatment planning but still understudied in academic literature. Methods: An expert-delineated cohort of 35 planning CTs was used for training of an nnU-net 3D-fullres/2D-ensemble model for autosegmentation of 20 different HN_LNL. Validation was performed in an independent test set (n=20). In a completely blinded evaluation, 3 clinical experts rated the quality of deep learning autosegmentations in a head-to-head comparison with expert-created contours. For a subgroup of 10 cases, intraobserver variability was compared to deep learning autosegmentation performance. The effect of autocontour consistency with CT slice plane orientation on geometric accuracy and expert rating was investigated. Results: Mean blinded expert rating per level was significantly better for deep learning segmentations with CT slice plane adjustment than for expert-created contours (81.0 vs. 79.6, p<0.001), but deep learning segmentations without slice plane adjustment were rated significantly worse than expert-created contours (77.2 vs. 79.6, p<0.001). Geometric accuracy of deep learning segmentations was non-different from intraobserver variability (mean Dice per level, 0.78 vs. 0.77, p=0.064) with variance in accuracy between levels being improved (p<0.001). Clinical significance of contour consistency with CT slice plane orientation was not represented by geometric accuracy metrics (Dice, 0.78 vs. 0.78, p=0.572) Conclusions: We show that a nnU-net 3D-fullres/2D-ensemble model can be used for highly accurate autodelineation of HN_LNL using only a limited training dataset that is ideally suited for large-scale standardized autodelineation of HN_LNL in the research setting. Geometric accuracy metrics are only an imperfect surrogate for blinded expert rating.

Deep learning for brain metastasis detection and segmentation in longitudinal MRI data

Brain metastases occur frequently in patients with metastatic cancer. Early and accurate detection of brain metastases is very essential for treatment planning and prognosis in radiation therapy. To improve brain metastasis detection performance with deep learning, a custom detection loss called volume-level sensitivity-specificity (VSS) is proposed, which rates individual metastasis detection sensitivity and specificity in (sub-)volume levels. As sensitivity and precision are always a trade-off in a metastasis level, either a high sensitivity or a high precision can be achieved by adjusting the weights in the VSS loss without decline in dice score coefficient for segmented metastases. To reduce metastasis-like structures being detected as false positive metastases, a temporal prior volume is proposed as an additional input of the neural network. Our proposed VSS loss improves the sensitivity of brain metastasis detection, increasing the sensitivity from 86.7% to 95.5%. Alternatively, it improves the precision from 68.8% to 97.8%. With the additional temporal prior volume, about 45% of the false positive metastases are reduced in the high sensitivity model and the precision reaches 99.6% for the high specificity model. The mean dice coefficient for all metastases is about 0.81. With the ensemble of the high sensitivity and high specificity models, on average only 1.5 false positive metastases per patient needs further check, while the majority of true positive metastases are confirmed. The ensemble learning is able to distinguish high confidence true positive metastases from metastases candidates that require special expert review or further follow-up, being particularly well-fit to the requirements of expert support in real clinical practice.

ChrEnTranslate: Cherokee-English Machine Translation Demo with Quality Estimation and Corrective Feedback

We introduce ChrEnTranslate, an online machine translation demonstration system for translation between English and an endangered language Cherokee. It supports both statistical and neural translation models as well as provides quality estimation to inform users of reliability, two user feedback interfaces for experts and common users respectively, example inputs to collect human translations for monolingual data, word alignment visualization, and relevant terms from the Cherokee-English dictionary. The quantitative evaluation demonstrates that our backbone translation models achieve state-of-the-art translation performance and our quality estimation well correlates with both BLEU and human judgment. By analyzing 216 pieces of expert feedback, we find that NMT is preferable because it copies less than SMT, and, in general, current models can translate fragments of the source sentence but make major mistakes. When we add these 216 expert-corrected parallel texts back into the training set and retrain models, equal or slightly better performance is observed, which indicates the potential of human-in-the-loop learning. Our online demo is at https://chren.cs.unc.edu/ , our code is open-sourced at https://github.com/ZhangShiyue/ChrEnTranslate , and our data is available at https://github.com/ZhangShiyue/ChrEn

ChrEn: Cherokee-English Machine Translation for Endangered Language Revitalization

Cherokee is a highly endangered Native American language spoken by the Cherokee people. The Cherokee culture is deeply embedded in its language. However, there are approximately only 2,000 fluent first language Cherokee speakers remaining in the world, and the number is declining every year. To help save this endangered language, we introduce ChrEn, a Cherokee-English parallel dataset, to facilitate machine translation research between Cherokee and English. Compared to some popular machine translation language pairs, ChrEn is extremely low-resource, only containing 14k sentence pairs in total. We split our parallel data in ways that facilitate both in-domain and out-of-domain evaluation. We also collect 5k Cherokee monolingual data to enable semi-supervised learning. Besides these datasets, we propose several Cherokee-English and English-Cherokee machine translation systems. We compare SMT (phrase-based) versus NMT (RNN-based and Transformer-based) systems; supervised versus semi-supervised (via language model, back-translation, and BERT/Multilingual-BERT) methods; as well as transfer learning versus multilingual joint training with 4 other languages. Our best results are 15.8/12.7 BLEU for in-domain and 6.5/5.0 BLEU for out-of-domain Chr-En/EnChr translations, respectively, and we hope that our dataset and systems will encourage future work by the community for Cherokee language revitalization. Our data, code, and demo will be publicly available at https://github.com/ZhangShiyue/ChrEn